The long-term goal of the research project outlined in this application is to provide a detailed account of the mechanisms involved in the induction and expression of states of transplantation immunity. Our specific aims for the period of support requested here are: 1) To determine the effects on immune responses of presenting transplantation antigens in various forms. We are especially interested in comparing the responses to living tissues and those to tissues that have been devitalized by lyophilization, irradiation, treatment with glutaraldehyde, sonication, or heat. 2) To determine the effect on allograft responses of varying the nature of immunogenetic disparity between donors and recipients. 3) to determine the ways in which responses to graft antigens are initiated in lymph nodes draining the sites of grafts and the ways in which the cells in such stimulated nodes mature and migrate from the nodes to the vascular system and then to the graft. 4) To identify the site at which alloreactive effector cells become fully differentiated in vivo, and to determine the ability of such cells to circulate and cause graft destruction when transferred to syngeneic recipients. In conjunction with these transfer experiments we plan to determine the role of various subsets of lymphocytes in graft rejection. 5) To identify the site(s) at which memory cells specifically reactive with alloantigens are regenerated and to initiate the characterization of such cells. 6) To determine the mechanisms by which tissue and organ grafts containing mixtures of allogeneic and syngeneic cells are rejected. 7) To determine the extent to which MHC restriction influences the induction and expression of responses to minor H-antigens in vivo.